Does catheter-associated urinary tract infection increase ...



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Does catheter-associated urinary tract infection increase mortality in critically ill patients?

Christophe Clec’h, MD,

Medical-surgical intensive care unit, Avicenne teaching hospital, Bobigny, France.

Outcome of cancer and criticall illnesses, INSERM/UJF U823, Albert Bonniot institute, Rond point de la Chantourne, 38706 La Tronche Cedex, France.

Carole Schwebel, MD, medical intensive care unit, Albert Michallon teaching hospital, Grenoble, France.

Adrien Français, biostatistician, department of epidemiology, INSERM U823, Grenoble, France.

Dany Toledano, MD, medical intensive care unit, hospital of Gonesse, Gonesse, France.

Jean-Philippe Fosse, MD, medical-surgical intensive care unit, Avicenne teaching hospital, Bobigny, France.

Maïté Garrouste-Orgeas, MD, medical intensive care unit, Saint-Joseph hospital, Paris, France.

Elie Azoulay, MD, PhD, medical intensive care unit, Saint-Louis teaching hospital, Paris, France.

Christophe Adrie, MD, PhD, medical intensive care unit, Delafontaine hospital, Saint-Denis, France.

Samir Jamali, MD, medical-surgical intensive care unit, hospital of Dourdan, Dourdan, France.

Adrien Descorps-Declere, MD, surgical intensive care unit, Antoine Béclère teaching hospital, Clamart, France.

Didier Nakache, computer scientist, Conservatoire National des Arts et Métiers (CNAM), Paris, France.

Jean-François Timsit, MD, PhD, Outcome of cancer and criticall illnesses, INSERM/UJF U823, Albert Bonniot institute, Rond point de la Chantourne, 38706 La Tronche Cedex, France.

Yves Cohen, MD, medical-surgical intensive care unit, Avicenne teaching hospital, Bobigny, France.

On behalf of the OUTCOMEREA study group. Members of the OUTCOMEREA study group are listed in the appendix.

Potential conflicts of interest. All authors: no conflict to disclose.

Financial support. The French Ministry of Science and Technique (grant RNTS 03-2-93-0513).

Running head: impact of urinary tract infection.

Correspondence and requests for reprints should be addressed to:

Dr Christophe Clech, INSERM U823, team: Outcome of cancer and critical illnesses, Albert Bonniot Institue, Rond point de la Chantourne 38706 La Tronche Cedex.

Phone: +33148955249/ Fax: +33148955090. E-mail: christophe.clech@avc.aphp.fr

ABSTRACT

OBJECTIVE. To yield an accurate estimation of the association of catheter-associated urinary tract infection (CAUTI) with intensive care unit and hospital mortality, controlling for major confounding factors.

DESIGN. Nested case-control study in a multi-center cohort (the OUTCOMEREA database).

SETTING. Twelve French medical or surgical intensive care units.

PATIENTS. All patients admitted between January 1997 and August 2005 requiring the insertion of an indwelling urinary catheter. Patients who developed CAUTI (cases) were matched to controls according to the following criteria: sex, age ± 10 years, SAPS (Simplified Acute Physiology Score) II score ± 10 points, length of urinary tract catheterization, and presence or absence of diabetes mellitus. The association of CAUTI with ICU and hospital mortality was assessed using conditional logistic regression.

RESULTS. Of the 3281 patients with an indwelling urinary catheter, 298 (9 %) developed at least one episode of CAUTI. The incidence density of CAUTI was 12.9 per 1000 catheterization days. Crude ICU and hospital mortality rates were higher in patients with than in those without CAUTI (32% vs 25%, p = 0.02, and 43% vs 30%, p < 0.01, respectively). After matching and adjustment, CAUTI was no longer associated with increased mortality (ICU mortality: odds ratio -OR-: 0.846, 95% confidence interval -CI-: 0.659-1.086, p = 0.19; hospital mortality: OR: 0.949, 95% CI: 0.763-1.181, p = 0.64).

CONCLUSION. After careful controlling for confounding factors, CAUTI was not associated with an excess in either ICU or hospital mortality in our population of critically ill patients.

INTRODUCTION

Urinary tract infections (UTI) are the most common infection acquired in hospitalized adult patients, accounting for 30-40 % of all nosocomial infections.1, 2 Within the hospital, the intensive care unit (ICU) has the highest prevalence of UTI (8-21%), more than 95 % of which being associated with the presence of an indwelling urinary catheter. 3, 4

Although catheter-associated urinary tract infection (CAUTI) being a very common issue, its link with mortality remains controversial. In a large cohort study conducted in 1982, Platt et al. reported a significantly higher risk of hospital mortality in patients with CAUTI.5 Two more recent studies found similar results.6, 7 Three other studies, however, reported opposite results stating that CAUTI did not increase mortality.8-10 Discrepant results of these studies could be ascribable to patients’ baseline heterogeneousness and subsequent in-hospital events, which may have confounded the link between CAUTI and mortality.

Knowing the real impact of CAUTI on patients’ outcome is undoubtedly necessary to decide whether specific treatments are required. Particularly, it would help resolve some important issues frequently arising in the ICU such as the need to change the urinary catheter or give antibiotics.

Thus, we performed this study to yield a more accurate estimation of the association of CAUTI with ICU and hospital mortality, matching patients on the probability of ICU-acquired UTI, and further controlling for major confounding factors.

METHODS

Study Design and Data Source

We conducted a nested case-control study in a multi-center cohort (the OUTCOMEREA database) from January 1997 to August 2005. The database, fed by 12 French ICUs, is designed to record daily disease severity and occurrence of iatrogenic events. A random sample of patients older than 16 years and having ICU stays longer than 24 h was entered into the database each year. Briefly, each participating ICU could choose between two sampling methods: (1) consecutive admissions in n randomized beds or (2) consecutive admissions in a randomized month.

In accordance with French law, the OUTCOMEREA database was declared to and approved by the Commission Nationale de l’Informatique et des Libertés (CNIL). Since routine collection of clinical and paraclinical data did not modify patients’ management in anyway and statistical analyses were processed anonymously, informed consent for participation in the study was waived.

Method of data collection

Senior physicians of the participating ICUs closely involved in establishing the database collected data daily. For each patient, the investigators entered the data into a computer case-report form using the data capture software VIGIREA( (OUTCOMEREATM, Rosny-sous-Bois, France) and imported all records to the OUTCOMEREA( database. All codes and definitions were written before data collection.

Quality of the database

The data capture software immediately conducted an automatic check of most of the variables entered by the investigators. Multiple automatic checking of internal consistency generated queries that were sent to the ICUs before the new data were incorporated into the database. At each participating ICU, the quality control procedure involved having a senior physician from another participating ICU check a 2% random sample of study data. Kappa coefficients ranged from 0.5 to 0.9 for qualitative variables, and inter-rater correlation coefficients ranged from 0.67 to 1 for clinical variables, severity scores, and organ dysfunction scores.

The lowest kappa coefficient was obtained for Mc Cabe score. The lowest inter-rater correlation was obtained for lactate level on day 3. Otherwise, the kappa coefficient was always higher than 0.62 for qualitative variables, and the inter-rater coefficient ranged between 0.72 and 0.99 for quantitative variables. In particular, it ranged between 0.78 and 0.91 for severity and organ dysfunction scores, and was 0.99 for duration of mechanical ventilation, ICU and hospital stay.”

Study Population and definitions

All patients in the database were eligible. Patients with UTI before insertion of the urinary catheter, and patients without urinary catheter were excluded.

Patients were cautiously screened for CAUTI. Specimens were systematically collected for urine cultures, either on a weekly basis, or if a new sepsis occurred. CAUTI was deemed present when urine cultures yielded at least 103 cfu/ml of one or two microorganisms.11, 12 A bacteremic/fungemic CAUTI was defined as a CAUTI with positive blood cultures with the same microorganism within a 48 hours period.

Patients who developed CAUTI represented the cases. In patients who developed several episodes of CAUTI, only the first episode was included in the analysis. Controls were selected among the remaining patients. Cases were matched to controls on the basis of predicted mortality and known risk factors for ICU-acquired UTI,13-17 using the algorithm available on line at: . More precisely, matching criteria were as follows: sex, age ± 10 years, SAPS (Simplified Acute Physiology Score) II ± 10 points, presence or absence of diabetes mellitus, and length of urinary tract catheterization. In addition, we imposed that the time to CAUTI from the insertion of the urinary catheter in the cases be less or equal than the length of urinary tract catheterization of their respective controls.

Data Collection

The following data were collected: age, sex, Mc Cabe class (class 1, no fatal underlying disease; class 2, underlying disease fatal within 5 years; class 3, underlying disease fatal within 1 year),18 comorbidities assessed according to the Acute Physiology and Chronic Health Evaluation (APACHE) II definitions,19 severity of illness at ICU admission and daily during the ICU stay assessed using the SAPS II score,20 the Sequential Organ Failure Assessment (SOFA) score 21 and the Logistic Organ Dysfunction (LOD) score,22 admission category (medical, scheduled surgery, or unscheduled surgery), admission diagnosis, whether the patient was transferred from a ward (defined as a stay in an acute-bed ward ≥24 hours immediately before ICU admission), lengths of ICU and hospital stays, and vital status at ICU and hospital discharge. Invasive procedures (placement of an arterial or central venous catheter, and endotracheal intubation), treatments of organ failure (catecholamine infusion, mechanical ventilation), and antibiotic use were also recorded.

Statistical Analyses

Comparisons between patients in the whole cohort were based on chi-square tests for categorical data and on Wilcoxon’s test for continuous data.

Assuming an ICU mortality of 30% in patients without CAUTI, and that CAUTI would occur in more than 250 patients, we calculated that 3 controls per patient with CAUTI would be necessary to unmask a difference in the odds ratio of mortality of 1.5 with an alpha risk of 5% and a power of 80%.

Comparisons between matched patients were first based on bivariate conditional logistic regression. Multivariate conditional logistic regression was then used to examine the association between CAUTI and ICU and hospital mortality, adjusting for potential confounding variables (ie, variables that had a p value ≤.10 in bivariate analysis). Wald (2 tests were used to determine the significance of each variable. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated for each parameter estimate.

A p value less than .05 was considered significant. Analyses were computed using the SAS 9.1 software package (SAS Institute, Cary, NC, USA).

RESULTS

Study population

Of the 4811 OUTCOMEREA database patients, 64 (1.3 %) had urinary tract infection on ICU admission and were excluded. Among the remaining 4747 patients, 3281 (69.1 %) had an indwelling urinary catheter and 298 (9%) had CAUTI. The overall incidence density of CAUTI was 12.9 per 1000 catheterization days. Bacteremic/fungemic CAUTI occurred in 4 cases for an overall incidence density of 0.17 per 1000 catheterization days. The median [interquartile range] time to CAUTI was 11 [6-19] days from the insertion of the urinary catheter.

On the day CAUTI occurred, 64 (21.5 %) patients required catecholamine infusion and 198 (66.4 %) patients were receiving antibiotics for extra-urinary sepsis. General characteristics of study patients are shown in table 1.

Several factors present at admission or within 48 hours of ICU stay were associated with an increased risk of CAUTI. Patients with CAUTI, as compared to those without CAUTI, were older, had higher SAPS II scores and were more likely to have received catecholamine infusion or mechanical ventilation during the first 48 hours of ICU stay (table 1).

Microbiology

Two hundred thirty-two (77.8%) patients had one episode of CAUTI, 44 (14.8%) patients had two episodes, and 22 (7.4%) patients had three or more episodes. Most episodes (93.6%) were monomicrobial. Microorganisms retrieved from urine cultures are listed in table 2. Microorganisms identified both in urine and blood cultures were: Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli, and Candida albicans.

Matching

Among the 298 patients with CAUTI, 273 (91.6%) were matched successfully to 896 controls for all matching criteria. Unmatched patients were younger and had longer length of urinary catheterization than matched patients but had similar SAPS II and LOD scores at ICU admission.

Cases were less likely than controls to have received antibiotics within 72 hours before CAUTI (or the corresponding day in controls). General characteristics and in-ICU events potentially associated with mortality in cases and controls are shown in table 3.

Outcomes

Overall, ICU and hospital mortality rates in patients with and without CAUTI were 32% vs 25% (p = .02) and 43% vs 30% (p < .01), respectively. Lengths of ICU and hospital stays (median in days, interquartile range) were significantly increased in patients with than in those without CAUTI (28 (16-45( vs 7 (4-13(, p ................
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